Laboratory Medicine

Question 1

van der waals

Answer 1

shifting electrons density in areas of a molecule or in a molecule as a whole results in the generation of transient positive or negative charges. these areas interact with transient areas of opposite charge on another molecule

Question 2

hydrogen bond

Answer 2

hydrogen atoms bound to N or O become more positively polarized, allowing them to bond to more negatively polarized atoms such as O, N, or S

Question 3

ionic

Answer 3

atoms with an excess of electrons (so neg charge) are attracted to atoms with a deficiency of electrons (pos charge)

Question 4

covalent

Answer 4

two bonding atoms share electrons

Question 5

Factors that affect interactions

Answer 5

• hydrophobicity
• hydrophilicity
• pka of AA near binding site
• conformation
• stereochemistry

Question 6

induced fit

Answer 6

binding of the drug to the receptor causes conformational change and increased affinity
-drug binding improve quality of binding interaction but also alter the active of the receptor

Question 7

active site

Answer 7

binding site of drugs on receptor

Question 8

specificity

Answer 8

determined by factors of:

• drug and receptor structure
• chemical forces influencing drug-receptor interaction
• drug solubility in water and in the plasma membrane
• function of receptor in cellular environment

Question 9

selectivity

Answer 9

the idea that drugs only interact with molecular target that causes desired therapeutic effects but not with molecular targets with cause unwanted effects

Question 10

selectivity conferred by:

Answer 10

• cell-type specificity of receptor subtypes

- cell-type specificy of receptor-effector coupling

Question 11

how does cell-type specificity of receptor subtypes effect selectivity

Answer 11

the more restricted the cell-type distribution of the receptor targeted by a particular drug , the more selecitve the drug is likely to by

Question 12

how does cell-type specificity of receptor-effector coupling effect selectivity

Answer 12

the more receptor-effector coupling mechanisms differ among the various cell types that express a particular molecule target for a drug, the more selective the drug is likely to be

Question 13

full agonists

Answer 13

bind to and activate targets to max extent

Question 14

partial agonists

Answer 14

produce a submaximal response upon binding to their targets

Question 15

inverse agonists

Answer 15

cause constitutively active targets to become inactive

Question 16

competitive anatagonists

Answer 16

drugs that directly block the binding site of a physiological agonist

Question 17

non-competitive antagonists

Answer 17

drugs that bind to other sites on the target molecule and thereby prevent the conformational change required for receptor activation (or inactivation)

Question 18

Transmembrane linked to intracellular and G protein describe the general GPCR activiation

Answer 18

7 transmem regions with single polypep chain

• agonist to receptor
• alpha subunit exchanges GDP->GTP
• alpha GTP disassociates from betagamma and diffuses along inner leaflet of the plasma membrane to interact with a number of different effectors
• signals mediated by g proteins are terminated by hydrolysis of GTP->GDP

Question 19

Some effectors of gPCR

Answer 19

• PLC cleaves PIPz to DAG (smooth m contraction) and IP3 (inc cytoplasmic ca)
• adenylyl cyclase activated cAMP
• ion channels
• proteins

Question 20

Major G proteins and examples of their actions

Answer 20

• G-stim (Gs): activiates ca2 channels, acitivate adenylyl cyclase
• G-inhibit (Gi): activates K channels, inhibits adenylyl cyclase
• Go: inhibits ca channels
• Gq: activates phospholipase C
• G12/13: diverse ion transporter interactions

Question 21

Transmembrane ion channels

Answer 21

• ligand gated
• voltage gated
• second messenger-regulated

Question 22

transmembrane with enzymatic cytosolic domain

Answer 22

• single-mem spanning
• work by phosphorylating AA residues with changes structure of protein and thus activates it
• tyrosine kinases

Question 23

drugs that do not fit the drug-receptor model

Answer 23

• osmotic diuretics

- antacids

Question 24

occupancy theory

Answer 24

the idea that a response emanates from a receptor only when it is occupied by an appropriate ligand

Question 25

spare receptor concept

Answer 25

when maximal response is chieved without 100% receptor occupancy; maximal effect is achieved at a lower dose of agonist than that required for receptor saturation (EC50>Kd)

Question 26

mechanisms thought to be responsible for discrepancy between the drug-receptor binding curve and the dose-response curve

Answer 26

• receptor could remain activiated after agonsit departs allowing one agonsit molecule to activate several receptors
• cell signaling pathway could allow for significant amplifaction of relatively small signal and activation of only a few receptors could be sufficient to produce a maximal response